Androgen receptor gene mutations are rarely associated with isolated penile hypospadias

Purpose: Hypospadias has no known single etiology but it has been linked to androgen insensitivity caused by mutations of the androgen receptor gene. The purpose of this study was to search ibr such mutations in cases of various degrees of isolated hypospadias to determine whether such an association exists and, if so, with any particular anatomical subgroup. Materials and Methods: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery was screened for mutations of the coding regions of the androgen receptor gene using single strand conformational polymorphism analysis. In cases with abnormal single strand conformational polymorphism findings sequence analysis of the deoxyribonucleic acid was performed to define the mutation. Results: A missense mutation of exon 2 of the androgen receptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amino acid residue 546 from proline to serine. No abnormalities were detected in the other 39 patients. Conclusions: Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.